Multiple Sclerosis (MS) is an autoimmune disease that arises when self reactive T cells attack healthy cells of the Central Nervous System (CNS). One of the major goals of animal models is to identify candidate therapeutics for treating human disease. Because the suppressive effects of IL- 10 on T cells and macrophages, MS therapies based on IL-10 are very promising candidates. Using a novel animal model in which IL-10 signaling has been eliminated through a deletion of the IL-10R1 gene, we will identify how IL-10 limits CNS autoimmunity. A fundamental understanding of how this cytokine influence T cell responses and CNS autoimmunity is critical to our ability correctly target its suppressive effects. In addition, MS patients harbor both CD4 and CD8 T cells specific for CNS proteins. Although many experiments indicate a prominent role for CD8 T cells in several autoimmune diseases, there are very few models to study CD8 T cells in CNS disease. Because of this, how CD8 T cells induce CNS autoimmunity is poorly understood. We have identified several CD8 T cells reactive to CNS proteins and will use one of these responses to identify their cellular targets in vivo. A thorough understanding of how CNS-reactive CD8 T cells function should greatly enhance our ability to identify and develop additional disease attenuating protocols. PUBLIC HEALTH RELEVANCE: Narrative Multiple Sclerosis is an autoimmune disease mediated by T cells within the CNS. MS lesions contain both CD4 and CD8 T cells. Understanding how CD8 T cell contribute to CNS autoimmunity will give new insight into MS disease mechanisms and suggest candidate therapies to treat human autoimmune disease. Because the suppressive effects of IL-10 on T cells and macrophages, MS therapies based on IL-10 are very promising candidates. A fundamental understanding of how this cytokine influence T cell responses and CNS autoimmunity is critical to our ability correctly target its suppressive effects.